Molded polymer-coated composite bone void filler improves tobramycin controlled release kinetics

• Published in: Journal of biomedical materials research. Part B, Applied biomaterials Vol. 102; no. 5; pp. 1074 - 1083
• Main Authors: Brooks, Benjamin D., Sinclair, Kristofer D., Davidoff, Sherry N., Lawson, Scott, Williams, Alex G., Coats, Brittany, Grainger, David W., Brooks, Amanda E.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Blackwell Publishing Ltd 01.07.2014; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacterial arthritis and osteitis; Bacterial diseases; Biological and medical sciences; Biomaterials; Biomedical materials; Bone Substitutes - chemistry; Bone Substitutes - pharmacokinetics; Bone Substitutes - pharmacology; bone void filler; Bones; Calcium Phosphates - chemistry; Calcium Phosphates - pharmacokinetics; Calcium Phosphates - pharmacology; Ceramics - chemistry; Ceramics - pharmacokinetics; Ceramics - pharmacology; controlled release; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Drug delivery systems; Fillers; Human bacterial diseases; implant infection; Infectious diseases; joint replacement; Materials research; Materials science; Medical sciences; Orthopedic surgery; Orthopedics; osteomyelitis; polycaprolactone; Polyesters - chemistry; Polyesters - pharmacokinetics; Polyesters - pharmacology; revision surgery; Staphylococcus aureus; Staphylococcus aureus - growth & development; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgical implants; Technology. Biomaterials. Equipments; tobramycin; Tobramycin - chemistry; Tobramycin - pharmacokinetics; Tobramycin - pharmacology; Voids; Prosthesis; Diseases of the osteoarticular system; implant infection; Lactone polymer; Composite material; Surgery; Osteitis; Aliphatic polymer; Biomaterial; Protein synthesis inhibitor; Polycaprolactone; Biomedical engineering; Bone substitute; joint replacement; Reoperation; Implant; Controlled release form; Control release polymer; bone void filler; Coated material; Infection; osteomyelitis; Antibiotic; controlled release; Treatment; Aminoglycoside; revision surgery; Kinetics; Tobramycin; Antibacterial agent; polycaprolactone; tobramycin
• ISSN: 1552-4973; 1552-4981
• DOI: 10.1002/jbm.b.33089

Infection remains a significant problem associated with biomedical implants and orthopedic surgeries, especially in revision total joint replacements. Recent advances in antibiotic-releasing bone void fillers (BVF) provide new opportunities to address these types of device-related orthopedic infections that often lead to substantial economic burdens and reduced quality of life. We report improvements made in fabrication and scalability of an antibiotic-releasing polycaprolactone-calcium carbonate/phosphate ceramic composite BVF using a new solvent-free, molten-cast fabrication process. This strategy provides the ability to tailor drug release kinetics from the BVF composite based on modifications of the inorganic substrate and/or the polymeric component, allowing extended tobramycin release at bactericidal concentrations. The mechanical properties of the new BVF composite are comparable to many reported BVFs and validate the relative homogeneity of fabrication. Most importantly, fabrication quality controls are correlated with favorable drug release kinetics, providing bactericidal activity to 10 weeks in vitro when the polycaprolactone component exceeds 98% w/w of the total polymer fraction. Furthermore, in a time kill study, tobramycin-releasing composite fragments inhibited S. aureus growth over 48 h at inoculums as high as 10(9) CFU/mL. This customizable antibiotic-releasing BVF polymer-inorganic biomaterial should provide osseointegrative and osteoconductive properties while contributing antimicrobial protection to orthopedic sites requiring the use of bone void fillers.